We are studying the properties of isolated retinal and cerebral capillaries from the standpoint of tissue culture, biochemistry, and light and electron microscopic anatomy. The goal of our research is to understand normal physiology of these capillaries as well as pathology, particularly as it relates to disease states such as diabetes mellitus. Tissue culture is being used to determine what factors stimulate proliferation of the various types of cells in these capillaries and in an effort to obtain pure populations of cultured intramural pericytes and endothelial cells. Biochemical studies are specifically directed at the enzymes of the sorbitol pathway and at studies of basement membrane and collagen biosynthesis. Anatomical investigations involve, first, characterization by light microscopy of retinal and cerebral capillaries in normal and diabetic humans, and second, investigation of the surface properties of these vessels by scanning electron microscopy also in normal diabetic individuals.